Reference Interval for Pulse Oxygen Saturation in Neonates at Different Altitudes: A Systematic Review.

Introduction: The reference interval for pulse oxygen saturation (SpO2) in neonates born at high altitudes has not been defined to date. The purpose of this study was to systematically review published studies and determine the reference interval of SpO2 in neonates at different altitudes. Methods: Databases of PubMed, Embase, Cochrane Library, Clinicaltrials.Gov, Chinese National Knowledge Infrastructure Database, Wanfang Database, Chinese Science Technology Journals Database, and Chinese Clinical Trial Registry were searched for studies reporting SpO2 in healthy neonates at different altitudes. Retrieval time was from inception of the database to August 16, 2021. The Agency for Healthcare Research and Quality checklist was used to evaluate the quality of studies. Python v3.8 was used to analyze the data. This systematic review was drafted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Seven cross-sectional studies, published between 1991 and 2020, were identified. They were from US, Mexico, Israel, Ecuador, and China. Three studies were rated as high quality and four as moderate quality. The mean SpO2 (with standard deviation or standard error) of neonates born in 40 different altitudes (ranging from 25 meters to 3,100 meters) were obtained. The prediction equation for calculation of the lower limit of the reference interval was established, and the reference intervals for SpO2 at different altitudes were determined. Conclusions: In healthy neonates, the lower limit of the reference interval of SpO2 decreases with increase in altitude. High-quality prospective studies are need to confirm our findings.

Association of the Aldose Reductase-106TT Genotype with Increased Risk for Diabetic Retinopathy in the Chinese Han Population: An Updated Meta-Analysis.

PURPOSE: A meta-analysis was conducted to assess the effects of the aldose reductase (ALR) C-106T polymorphism on the risk for development of diabetic retinopathy (DR) in the Chinese population. MATERIALS AND METHODS: Relevant studies were identified using PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) through 21 March 2015. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. RESULTS: This meta-analysis identified 11 studies, including 1386 DR cases, 1594 diabetes mellitus (DM) control cases, and 472 healthy control cases. In the overall analysis, a non-significant association between the ALR C(-106)T polymorphism and DR was found in the Chinese population. In subgroups stratified by ethnicity, significantly increased risks for DR in association with ALR C(-106)T variants were found in the Chinese Han population. When compared with healthy controls, we found the following associations: T versus C (OR, 1.63; 95%CI, 1.23-2.17), TT versus CC (OR, 2.04; 95%CI, 1.03-4.02), and TT + CT versus CC (OR, 1.82; 95%CI, 1.28-2.57). CONCLUSIONS: Our meta-analysis showed that ALR C-106T variants appear to influence the risk for DR in Chinese Han persons. Studies with larger sample sizes and wider population spectra are warranted to verify this finding.

Simvastatin induces caspase-dependent apoptosis and activates P53 in OCM-1 cells.

Simvastatin is a cholesterol-lowering drug which exhibits numerous pleiotropic effects including anti-cancer activity. Yet, the anti-cancer effects in choroidal melanoma remain poorly characterized. Therefore, in this study, we investigated the effects of simvastatin on OCM-1 cells growth, apoptosis and cycle. Simvastatin showed an inhibitory effects on OCM-1 cells viability in dose-dependent (2-10 µM) and time-dependent (24-72 h) manner. Further study suggested that simvastatin-induced inhibition OCM-1 cells proliferation was associated with G1 phase arrest, decreased protein and mRNA expression of proliferation marker cyclin D1, cyclin E, cyclin dependent kinase (CDK)2 and increased expression of CDK inhibitory protein P21. In addition, simvastatin resulted in an increase in levels of reactive oxygen species (ROS) in OCM-1 cells and simvastatin significantly triggered apoptosis in OCM-1 cells, which was characterized by increased chromatin condensation, activation of caspase-9 and cleaved-caspase-3, increased expression mitochondrion-related apoptosis protein of P53, Bax and decreased expression of Bcl2 and iASPP. Collectively, our study demonstrated that simvastatin can efficiently inhibit proliferation and induce apoptosis in OCM-1 cells.

[Changes of expression of HIF-1alpha in the human retinal pigment epithelium induced by hypoxia].

OBJECTIVE: To investigate the expression of HIF-1alpha in human retinal pigment epithelium (hRPE) induced by hypoxia at different time points and to study the mechanism of choroidal neovascularization. METHODS: hRPE were isolated, cultured and identified. The changes of level of mRNA and protein of HIF-1alpha in hRPE at different time points after exposed to hypoxia were measured by semi-quantitative RT-PCR and immunofluorescence techniques. RESULTS: A significant increase of HIF-1alpha level in cultured hRPE was induced by hypoxia. After 8 hours exposed to hypoxia, the level of HIF-1alpha in the hRPE reached a peak and sustained for more than 16 hours. After a prolonged exposure to hypoxia, the morphology of hRPE began to change and the HIF-1alpha level was decreased. CONCLUSIONS: The level of HIF-1alpha in hRPE rises obviously after exposed to hypoxia. This may play a role in the occurrence of choroidal neovascularization.

Inhibition of vascular endothelial growth factor gene expression by T7-siRNAs in cultured human retinal pigment epithelial cells.

BACKGROUND: Retinal pigment epithelial (RPE) cells play an important role in the occurrence of choroidal neovascularization (CNV). Vascular endothelial growth factor (VEGF) as a positive regulatory growth factor is produced by the RPE in an autocrine or paracrine manner, promoting CNV development. Duplexes of 21 nt RNAs, known as short interfering RNAs (siRNAs), efficiently inhibit gene expression by RNA interference when introduced into mammalian cells. We searched for an efficient siRNA to interfere with VEGF expression in RPE cells and shed light on the treatment of CNV. METHODS: Human primary RPE (hRPE) cells were cultured and identified. Three pairs of siRNAs were designed according to the sequence of VEGF 1-5 extrons and synthesized by T7 RNA polymerase transcription in vitro. To evaluate the inhibitory activity of T7-siRNAs, hRPE cells were transfected via siPORT Amine. The interfering effect of T7-siRNAs in hRPE cells was examined by semiquantitative reverse transcription-polymerase chain reaction and immunofluorescence. RESULTS: Three pairs of T7-siRNAs synthesized by in vitro transcription with T7 RNA polymerase suppressed VEGF gene expression with efficiency from 65% to 90%. T7-siRNA (B), targeted region at 207 nt to 228 nt and double stranded for 21 nt with 2 nt UU 3' overhangs, was the most effective sequence tested for inhibition of VEGF expression in hRPE cells. Compared with nontransfected cells, the mean fluorescence in hRPE cells transfected with T7-sRNAs was significantly less (P < 0.01). siRNA with a single-base mismatch and ssRNA(+) did not show suppressing effect. Furthermore, it was found that siRNAs had a dose dependent inhibitory effect (5 to 10 pmol). CONCLUSION: T7-siRNA can effectively and specifically suppress VEGF expression in hRPE cells and may be a new way to treat CNV.

Effects of denervation on cell cycle control in laryngeal muscle.

Denervation of skeletal muscle is thought to lead to an accelerated proliferation of myogenic stem cells known as satellite cells. The transition of these cells from a quiescent to a proliferative state is thought to require satellite cells to enter the cell cycle and replicate. Little is known about the expression of genes associated with cell cycle control, and so the objective of this study was to examine the effects of denervation and reinnervation of the posterior cricoarytenoid (PCA) muscle on key cell cycle genes. Female Sprague-Dawley rats were assigned to control, denervated, or reinnervated groups. Animals were killed at 7, 14, and 30 days after ligation of the recurrent laryngeal nerve. The PCA muscle was then analyzed for changes in the messenger RNA levels of key genes associated with cell cycle control, differentiation, and proliferation. Cyclin D1 is a key gene responsible for initiating progression of the cell cycle from G1 to S phase. Interestingly, neither denervation nor reinnervation affected the expression of this gene. In contrast, we found large increases in key cell cycle inhibitors (p21 and the growth arrest and DNA destruction 45 [GADD45] gene) in both the denervated and reinnervated groups. We interpret the increases in these cell cycle inhibitors to reflect (1) an inhibition of satellite cell proliferation and/or (2) a special form of apoptosis that results in the loss of myonuclei known to occur under atrophic conditions. To our knowledge, this is the first study to examine the effects of denervation on cell cycle regulation.

The plasticity of denervated and reinnervated laryngeal muscle: focus on single-fiber myosin heavy-chain isoform expression.

No studies have examined the effects of denervation on the single-fiber distribution of myosin heavy-chain (MyHC) isoforms in laryngeal muscle. The fast type IIB MyHC isoform represents the largest proportion of the myosin pool in the posterior cricoarytenoid (PCA) and the thyroarytenoid (TA) muscles. However, the fast type IIB MyHC isoform is distributed differently at the single-fiber level. Hence, we hypothesized that denervation would result in markedly different patterns of MyHC isoform expression at the single-fiber level. To test this hypothesis, we assigned animals to the following 3 groups: (1) control group; (2) denervation group; or (3) reinnervation group. Animals were killed 7, 14, 30, 90, and 180 days after denervation or reinnervation. Subsequently, the distribution of MyHC isoforms were electrophoretically determined in approximately 7200 single fibers. There were 4 key findings to emerge from this study: (1) The MyHC isoform profile of the PCA muscle, at both the whole-muscle and single-fiber level, is more malleable than that of the TA muscle. (2) In the PCA and TA muscles, denervation produced some similar changes, resulting in a large increase in the pool of fibers coexpressing fast type IIX and IIB MyHC isoforms. (3) Reinnervation of the TA muscle produced significant alterations in the single-fiber distribution of MyHC isoforms while having little effect on the whole-muscle MyHC isoform composition. (4) Since the transitions in MyHC isoform expression associated with denervation were limited primarily to fast type IIB to fast type IIX, we postulate that only minor reductions in muscle function would result (as defined by maximum shortening velocity and the force-velocity relationship).

Single-fiber myosin heavy chain polymorphism: how many patterns and what proportions?

Previous studies have reported the existence of skeletal muscle fibers that coexpress multiple myosin heavy chain isoforms. These surveys have usually been limited to studying the polymorphic profiles of skeletal muscle fibers from a limited number of muscles (i.e., usually <4). Additionally, few studies have considered the functional implications of polymorphism. Hence, the primary objective of this study was to survey a relatively large number of rat skeletal muscle/muscle regions and muscle fibers (n approximately 5,000) to test the hypothesis that polymorphic fibers represent a larger fraction of the total pool of fibers than do so-called monomorphic fibers, which express only one myosin heavy chain isoform. Additionally, we used Hill's statistical model of the force-velocity relationship to differentiate the functional consequences of single-fiber myosin heavy chain isoform distributions found in these muscles. The results demonstrate that most muscles and regions of rodent skeletal muscles contain large proportions of polymorphic fibers, with the exception of muscles such as the slow soleus muscle and white regions of fast muscles. Several muscles were also found to have polymorphic profiles that are not consistent with the I<-->IIA<-->IIX<-->IIB scheme of muscle plasticity. For instance, it was found that the diaphragm muscle normally contains I/IIX fibers. Functionally, the high degree of polymorphism may 1) represent a strategy for producing a spectrum of contractile properties that far exceeds that simply defined by the presence of four myosin heavy chain isoforms and 2) result in relatively small differences in function as defined by the force-velocity relationship.